Established from human or mouse early embryos, embryonic stem cells (ES cells) are capable of being cultured for a long time while maintaining their potential for differentiating into all types of cells found in a living organism. With this feature, human ES cells are expected to serve for cell transplantation therapies for many diseases, including Parkinson's disease, juvenile diabetes, and leukemia. However, ES cell transplantation poses the problem of causing rejections as with organ transplantation. Additionally, not a few people oppose the use of ES cells established with the destruction of a human embryo, from an ethical viewpoint.
If the dedifferentiation of a patient's somatic cells is induced to establish cells possessing pluripotency and proliferating capability similar to those of an ES cell (herein these cells are referred to as “induced pluripotent stem cells” (iPS cells), and sometimes referred to as “embryonic stem cell-like cells” or “ES-like cells”), the established cells will be useful as ideal pluripotent cells that do not pose the problems of rejections and ethical issues. In recent years, it has been reported that iPS cells can be produced from mouse and human differentiated cells, arousing great attention (International Patent Application Publication No. WO2007/69666; Cell, 126, pp. 663-676, 2006; Cell, 131, pp. 861-872, 2007; Science, 318, pp. 1917-1920, 2007; Nature, 451, pp. 141-146, 2008).
All these methods comprise the step of introducing a plurality of particular nuclear reprogramming factors (e.g., in Cell, 126, pp. 1-14, 2006, 4 factors are used: Oct3/4, Sox2, Klf4, and c-Myc) into a somatic cell to achieve reprogramming, which step involves the use of a retrovirus or a lentivirus for the purpose of introducing the genes that encode the nuclear reprogramming factors into a somatic cell efficiently. However, since gene delivery using a viral vector involves safety issues, there is a demand for developing a method of producing iPS cells without using a viral vector.